Cited by 468HIV Research and TreatmentVirus-based gene therapy researchGenomics and Chromatin Dynamics

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The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation

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Jordan, Albert, Defechereux, Patricia, Verdin, Eric·2001·The EMBO Journal

DOI 10.1093/emboj/20.7.1726PMC PMC145503

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Abstract

Because of the heterogeneity of chromatin, the site of integration of human immunodeficiency virus (HIV) in the genome could have dramatic effects on its transcriptional activity. We have used an HIV-1-derived retroviral vector, in which the green fluorescent protein is under the control of the HIV promoter, to generate by infection 34 Jurkat clonal cell lines each containing a single integration of the HIV-1 vector. In the absence of Tat, a 75-fold difference in expression level between the highest and lowest expressing clones was observed. Basal promoter activity was low in 80% of the clones and moderate to high in the remaining 20% of clones. We found that differences in expression levels are due to the integration site and are not controlled by DNA methylation or histone acetylation. Tat activated transcription in each clone, and an inverse correlation was observed between basal transcriptional activity and inducibility by Tat. These observations demonstrate that the chromatin environment influences basal HIV gene expression and that the HIV Tat protein activates transcription independently of the chromatin environment.

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Authors: Jordan, A., Defechereux, P., & Verdin, E.
Affiliations: University of California, San Francisco (US)
Corresponding author: Verdin, Eric
ORCID: Jordan, Albert
Verdin, Eric
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2001-04-02
Volume: 20
Issue: 7
Pages: 1726-1738
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1093/emboj/20.7.1726
PMC: PMC145503
OpenAlex: W1964660012
Cited by: 467
References: 48
Citations by year: 2026: 13 · 2025: 21 · 2024: 19 · 2023: 18 · 2022: 15 · 2021: 15 · 2020: 21 · 2019: 21 · 2018: 20 · 2017: 26 · 2016: 25 · 2015: 27 · 2014: 14 · 2013: 15 · 2012: 14
FWCI: 6.25
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Belgian American Educational Foundation
National Institutes of Health
National Institute of General Medical Sciences (GM51671-05A2, R01GM051671)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: Tat transactivation, basal transcription, chromatin environment, HIV-1 promoter, retroviral vectors, Jurkat cells, DNA methylation, histone acetylation, HIV gene expression
MeSH terms: Binding Sites, Cell Line, Transformed, Genetic Vectors, HeLa Cells, Humans, Hydroxamic Acids, Promoter Regions, Genetic, Tetradecanoylphorbol Acetate, Transcription, Genetic, HIV-1, Transcriptional Activation, Gene Products, tat, Genome, Human, Gene Expression Regulation, Viral, HIV Long Terminal Repeat, Virus Integration, Cyclin-Dependent Kinases, Jurkat Cells, DNA Methylation, Cyclin-Dependent Kinase 9, tat Gene Products, Human Immunodeficiency Virus, Histone Deacetylase Inhibitors

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The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation

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